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[PMID]:29409851
[Au] Autor:Tan M; Li G; Qi S; Liu X; Chen X; Ma J; Zhang D; Han M
[Ad] Endereço:College of Horticulture, Northwest A & F University, Yangling, Shaanxi 712100, China.
[Ti] Título:Identification and expression analysis of the IPT and CKX gene families during axillary bud outgrowth in apple (Malus domestica Borkh.).
[So] Source:Gene;651:106-117, 2018 Apr 20.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Cytokinins (CKs) play a crucial role in promoting axillary bud outgrowth and targeting the control of CK metabolism can be used to enhance branching in plants. CK levels are maintained mainly by CK biosynthesis (isopentenyl transferase, IPT) and degradation (dehydrogenase, CKX) genes in plants. A systematic study of the IPT and CKX gene families in apple, however, has not been conducted. In the present study, 12 MdIPTs and 12 MdCKXs were identified in the apple genome. Systematic phylogenetic, structural, and synteny analyses were performed. Expression analysis of these genes in different tissues was also assessed. MdIPT and MdCKX genes exhibit distinct expression patterns in different tissues. The response of MdIPT, MdCKX, and MdPIN1 genes to various treatments (6-BA, decapitation and Lovastatin, an inhibitor of CKs synthesis) that impact branching were also investigated. Results indicated that most of the MdIPT and MdCKX, and MdPIN1 genes were upregulated by 6-BA and decapitation treatment, but inhibited by Lovastatin, a compound that effectively suppresses axillary bud outgrowth induced by decapitation. These findings suggest that cytokinin biosynthesis is required for the activation of bud break and the export of auxin from buds in apple tree with intact primary shoot apex or decapitated apple tree. MdCKX8 and MdCKX10, however, exhibited little response to decapitation, but were significantly up-regulated by 6-BA and Lovastatin, a finding that warrants further investigation in order to understand their function in bud-outgrowth.
[Mh] Termos MeSH primário: Alquil e Aril Transferases/genética
Genes de Plantas
Malus/genética
Oxirredutases/genética
[Mh] Termos MeSH secundário: Arabidopsis/genética
Compostos de Benzil/farmacologia
Mapeamento Cromossômico
Cromossomos de Plantas
Evolução Molecular
Flores/genética
Perfilação da Expressão Gênica
Regulação da Expressão Gênica de Plantas
Genoma de Planta
Lovastatina/farmacologia
Malus/enzimologia
Malus/crescimento & desenvolvimento
Família Multigênica
Filogenia
Reguladores de Crescimento de Planta
Purinas/farmacologia
Sintenia
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzyl Compounds); 0 (Plant Growth Regulators); 0 (Purines); 9LHU78OQFD (Lovastatin); EC 1.- (Oxidoreductases); EC 1.5.99.12 (cytokinin oxidase); EC 2.5.- (Alkyl and Aryl Transferases); EC 2.5.1.27 (adenylate isopentenyltransferase); KXG6A989PS (benzylaminopurine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180208
[St] Status:MEDLINE


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[PMID]:28583351
[Au] Autor:Yasuda K; Sugimoto H; Hayashi K; Takita T; Yasukawa K; Ohta M; Kamakura M; Ikushiro S; Shiro Y; Sakaki T
[Ad] Endereço:Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan; Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan.
[Ti] Título:Protein engineering of CYP105s for their industrial uses.
[So] Source:Biochim Biophys Acta;1866(1):23-31, 2018 01.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Cytochrome P450 enzymes belonging to the CYP105 family are predominantly found in bacteria belonging to the phylum Actinobacteria and the order Actinomycetales. In this review, we focused on the protein engineering of P450s belonging to the CYP105 family for industrial use. Two Arg substitutions to Ala of CYP105A1 enhanced its vitamin D 25- and 1α-hydroxylation activities by 400 and 100-fold, respectively. The coupling efficiency between product formation and NADPH oxidation was largely improved by the R84A mutation. The quintuple mutant Q87W/T115A/H132L/R194W/G294D of CYP105AB3 showed a 20-fold higher activity than the wild-type enzyme. Amino acids at positions 87 and 191 were located at the substrate entrance channel, and that at position 294 was located close to the heme group. Semi-rational engineering of CYP105A3 selected the best performing mutant, T85F/T119S/V194N/N363Y, for producing pravastatin. The T119S and N363Y mutations synergistically had remarkable effects on the interaction between CYP105A3 and putidaredoxin. Although wild-type CYP105AS1 hydroxylated compactin to 6-epi-pravastatin, the quintuple mutant I95T/Q127R/A180V/L236I/A265N converted almost all compactin to pravastatin. Five amino acid substitutions by two rounds of mutagenesis almost completely changed the stereo-selectivity of CYP105AS1. These results strongly suggest that the protein engineering of CYP105 enzymes greatly increase their industrial utility. This article is part of a Special Issue entitled: Cytochrome P450 biodiversity and biotechnology, edited by Erika Plettner, Gianfranco Gilardi, Luet Wong, Vlada Urlacher, Jared Goldstone.
[Mh] Termos MeSH primário: Actinobacteria/genética
Substituição de Aminoácidos
Proteínas de Bactérias/química
Sistema Enzimático do Citocromo P-450/química
Mutação
Engenharia de Proteínas/métodos
[Mh] Termos MeSH secundário: Actinobacteria/enzimologia
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Colecalciferol/metabolismo
Sequência Conservada
Sistema Enzimático do Citocromo P-450/genética
Sistema Enzimático do Citocromo P-450/metabolismo
Ferredoxinas/metabolismo
Expressão Gênica
Hidroxilação
Isoenzimas
Lovastatina/análogos & derivados
Lovastatina/metabolismo
Simulação de Acoplamento Molecular
Pravastatina/biossíntese
Streptomyces/enzimologia
Streptomyces/genética
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Ferredoxins); 0 (Isoenzymes); 1C6V77QF41 (Cholecalciferol); 1UQM1K0W9X (mevastatin); 57087-75-9 (putidaredoxin); 9035-51-2 (Cytochrome P-450 Enzyme System); 9LHU78OQFD (Lovastatin); EC 1.14.- (P450SU1 protein, Streptomyces griseolus); KXO2KT9N0G (Pravastatin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180208
[Lr] Data última revisão:
180208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170607
[St] Status:MEDLINE


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[PMID]:28802576
[Au] Autor:Melendez QM; Wooten CJ; Lopez D
[Ad] Endereço:Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technology Enterprise (BRITE), College of Arts and Sciences, North Carolina Central University, Durham, NC, 27707, USA.
[Ti] Título:Atorvastatin and lovastatin, but not pravastatin, increased cellular complex formation between PCSK9 and the LDL receptor in human hepatocyte-like C3A cells.
[So] Source:Biochem Biophys Res Commun;492(1):103-108, 2017 Oct 07.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Statins are the first-line treatment for hypercholesterolemic patients. Herein, the effects of three statins on complex formation between proprotein convertase subtilisin-kexin 9 (PCSK9) and the low density lipoprotein receptor (LDLR), a critical step for the PCSK9-dependent degradation of LDLR in the lysosome, were examined. Human hepatocyte-like C3A cells grown in control (containing 10% fetal bovine serum) or MITO+ (supplemented with BD™ MITO + serum extender) medium were also treated with atorvastatin (Atorv), lovastatin (Lov), or pravastatin (Prav) for 24 h. RNA and protein expression studies and determinations of PCSK9/LDLR complex formation were performed. As expected, the statins increased the expression of PCSK9 and LDLR independently of the medium employed. Interestingly, Atov and Lov caused increases in PCSK9/LDLR complex formation, whereas Prav decreased complex formation when compared to cells treated without drugs. These results may explain why Prav works better for statin intolerant patients than other statins such as Atorv and Lov.
[Mh] Termos MeSH primário: Atorvastatina Cálcica/farmacologia
Lovastatina/farmacologia
Pravastatina/farmacologia
Pró-Proteína Convertase 9/antagonistas & inibidores
Pró-Proteína Convertase 9/biossíntese
Receptores de LDL/antagonistas & inibidores
Receptores de LDL/biossíntese
[Mh] Termos MeSH secundário: Células Cultivadas
Seres Humanos
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, LDL); 48A5M73Z4Q (Atorvastatin Calcium); 9LHU78OQFD (Lovastatin); EC 3.4.21.- (PCSK9 protein, human); EC 3.4.21.- (Proprotein Convertase 9); KXO2KT9N0G (Pravastatin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170814
[St] Status:MEDLINE


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[PMID]:28789942
[Au] Autor:Kim ML; Sung KR; Shin JA; Young Yoon J; Jang J
[Ad] Endereço:Biomedical Research Center, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, South Korea.
[Ti] Título:Statins reduce TGF-beta2-modulation of the extracellular matrix in cultured astrocytes of the human optic nerve head.
[So] Source:Exp Eye Res;164:55-63, 2017 Nov.
[Is] ISSN:1096-0007
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Statins are cholesterol lowering drugs and have shown beneficial effects on glaucoma. With regard to the mechanism of statin action on glaucoma, we investigated the effects of statins on transforming growth factor-beta 2 (TGF-ß2)-induced expression of extracellular matrix (ECM) proteins in human astrocytes of the optic nerve head (ONH) lamina cribrosa (LC). By using primary human ONH astrocytes, we found that both simvastatin and lovastatin inhibited TGF-ß2-mediated expression of ECM proteins such as connective tissue growth factor, collagen I, fibronectin, and plasminogen activator inhibitor-1. Suppression of ECM related proteins is due to inhibition of Smad2/3 activation as statins inhibit TGF-ß2-induced Smad2 phosphorylation and Smad2/3 nuclear accumulation. In ONH astrocytes, TGF-ß2 does not induce MAPK activation. In this study we found an anti-fibrotic effect of statins in human astrocytes of the ONH and identified TGF-ß2 as a mediator of statin action, which may support a beneficial role for statins in blocking glaucomatous axonal damage induced by ECM remodeling.
[Mh] Termos MeSH primário: Astrócitos/efeitos dos fármacos
Matriz Extracelular/metabolismo
Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia
Disco Óptico/metabolismo
Fator de Crescimento Transformador beta2/fisiologia
[Mh] Termos MeSH secundário: Análise de Variância
Astrócitos/metabolismo
Células Cultivadas
Matriz Extracelular/efeitos dos fármacos
Proteínas do Olho/metabolismo
Seres Humanos
Lovastatina
Disco Óptico/citologia
Sinvastatina
Fator de Crescimento Transformador beta2/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Eye Proteins); 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors); 0 (Transforming Growth Factor beta2); 9LHU78OQFD (Lovastatin); AGG2FN16EV (Simvastatin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171012
[Lr] Data última revisão:
171012
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170810
[St] Status:MEDLINE


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[PMID]:28551243
[Au] Autor:Theunis M; Naessens T; Verhoeven V; Hermans N; Apers S
[Ad] Endereço:University of Antwerp, Natural Products & Food Research and Analysis (NatuRA), Universiteitsplein 1, B-2610 Antwerp, Belgium. Electronic address: mart.theunis@uantwerpen.be.
[Ti] Título:Development and validation of a robust high-performance liquid chromatographic method for the analysis of monacolins in red yeast rice.
[So] Source:Food Chem;234:33-37, 2017 Nov 01.
[Is] ISSN:0308-8146
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A robust analytical method, using reversed phase high-performance liquid chromatography with diode array detection, was developed and validated for the quantification of monacolins in red yeast rice bulk products. Tests on the composition of the extraction solvent, extraction time and the number of repetitions of extraction were evaluated with the aim of complete extraction of the monacolins and minimal transitions between the monacolins during analysis. Monacolin K (acid form), monacolin K (lactone form) and minor monacolin peaks were separated on a C18 column (250×4.6mm, 5µm) using acetonitrile/0.1% trifluoroacetic acid as the mobile phase. For the calibration curve of monacolin K (lactone form), a linear correlation in the range 6-119µg/mL was found. The precision of the method for time and concentration gave a relative standard deviation of less than 5%, which was deemed acceptable. The recovery of the method was 98.75%.
[Mh] Termos MeSH primário: Cromatografia Líquida de Alta Pressão
Lactonas/análise
Lovastatina/análise
Monascus
Oryza/química
[Mh] Termos MeSH secundário: Calibragem
Cromatografia de Fase Reversa
Fermentação
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Lactones); 9LHU78OQFD (Lovastatin)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170808
[Lr] Data última revisão:
170808
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170529
[St] Status:MEDLINE


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[PMID]:28511903
[Au] Autor:Caliceti C; Rizzo P; Ferrari R; Fortini F; Aquila G; Leoncini E; Zambonin L; Rizzo B; Calabria D; Simoni P; Mirasoli M; Guardigli M; Hrelia S; Roda A; Cicero AFG
[Ad] Endereço:Department of Chemistry "Giacomo Ciamician" - Alma Mater Studiorum, University of Bologna, Bologna, Italy; Centro Interdipartimentale di Ricerca Industriale Energia e Ambiente (CIRI EA) - Alma Mater Studiorum, University of Bologna, Bologna, Italy; Istituto Nazionale Biostrutture e Biosistemi (INBB)
[Ti] Título:Novel role of the nutraceutical bioactive compound berberine in lectin-like OxLDL receptor 1-mediated endothelial dysfunction in comparison to lovastatin.
[So] Source:Nutr Metab Cardiovasc Dis;27(6):552-563, 2017 Jun.
[Is] ISSN:1590-3729
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AND AIMS: Oxidized LDL (oxLDL) or pro-inflammatory stimuli lead to increased oxidative stress linked to endothelial dysfunction and atherosclerosis. The oxLDL receptor-1 (LOX1) is elevated within atheromas and cholesterol-lowering statins inhibit LOX1 expression. Berberine (BBR), an alkaloid extracted from plants of gender Berberis, has lipid-lowering and anti-inflammatory activity. However, its role in regulating LOX1-mediated signaling is still unknown. The aim of this study was to investigate the effect of BBR on oxLDL- and TNFα-induced endothelial dysfunction in human umbilical vein endothelial cells (HUVECs) and to compare it with that of lovastatin (LOVA). METHODS AND RESULTS: Cytotoxicity was determined by lactate dehydrogenase assay. Antioxidant capacity was measured with chemiluminescent and fluorescent method and intracellular ROS levels through a fluorescent dye. Gene and protein expression levels were assayed by qRT-PCR and western blot, respectively. HUVECs exposure to oxLDL (30 µg/ml) or TNFα (10 ng/ml) for 24 h led to a significant increase in LOX1 expression, effect abrogated by BBR (5 µM) and LOVA (5 µM). BBR but not LOVA treatment abolished the TNFα-induced cytotoxicity and restored the activation of Akt signaling. In spite of a low direct antioxidant capacity, both compounds reduced intracellular ROS levels generated by treatment of TNFα but only BBR inhibited NOX2 expression, MAPK/Erk1/2 signaling and subsequent NF-κB target genes VCAM and ICAM expression, induced by TNFα. CONCLUSIONS: These findings demonstrated for the first time that BBR could prevent the oxLDL and TNFα - induced LOX1 expression and oxidative stress, key events that lead to NOX, MAPK/Erk1/2 and NF-κB activation linked to endothelial dysfunction. CHEMICAL COMPOUNDS STUDIED IN THIS ARTICLE: Berberine (PubChem CID: 2353); Lovastatin (PubChem CID: 53232).
[Mh] Termos MeSH primário: Anti-Inflamatórios/farmacologia
Antioxidantes/farmacologia
Berberina/farmacologia
Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos
Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia
Lipoproteínas LDL/farmacologia
Lovastatina/farmacologia
Receptores Depuradores Classe E/agonistas
[Mh] Termos MeSH secundário: Sobrevivência Celular/efeitos dos fármacos
Células Cultivadas
Citoproteção
MAP Quinases Reguladas por Sinal Extracelular/metabolismo
Células Endoteliais da Veia Umbilical Humana/metabolismo
Células Endoteliais da Veia Umbilical Humana/patologia
Seres Humanos
Glicoproteínas de Membrana/metabolismo
NADPH Oxidase 2
NADPH Oxidases/metabolismo
NF-kappa B/metabolismo
Óxido Nítrico Sintase Tipo III/metabolismo
Estresse Oxidativo/efeitos dos fármacos
Espécies Reativas de Oxigênio/metabolismo
Receptores Depuradores Classe E/metabolismo
Transdução de Sinais/efeitos dos fármacos
Fator de Necrose Tumoral alfa/farmacologia
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); 0 (Antioxidants); 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors); 0 (Lipoproteins, LDL); 0 (Membrane Glycoproteins); 0 (NF-kappa B); 0 (OLR1 protein, human); 0 (Reactive Oxygen Species); 0 (Scavenger Receptors, Class E); 0 (Tumor Necrosis Factor-alpha); 0 (oxidized low density lipoprotein); 0I8Y3P32UF (Berberine); 9LHU78OQFD (Lovastatin); EC 1.14.13.39 (NOS3 protein, human); EC 1.14.13.39 (Nitric Oxide Synthase Type III); EC 1.6.3.- (CYBB protein, human); EC 1.6.3.- (NADPH Oxidase 2); EC 1.6.3.- (NADPH Oxidases); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170518
[St] Status:MEDLINE


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[PMID]:28490066
[Au] Autor:Gum SI; Nguyen PA; Lee JR; Han YH; Cho MK
[Ad] Endereço:Department of Pharmacology, College of Oriental Medicine, Dongguk University, Kyungju 780-714, South Korea.
[Ti] Título:The physico-chemical alteration of lovastatin and enhanced antioxidant effect of Bacillus subtilis fermented-red yeast rice product.
[So] Source:Food Chem;232:203-209, 2017 Oct 01.
[Is] ISSN:0308-8146
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Red yeast rice product (RYP) has been used as a food supplement because of its lipid lowering, and in food additives as a natural colorant. Lovastatin of RYP is a hypolipidemic commercial drug. To enhance the beneficial effects of RYP, we performed a bioconversion with Bacillus subtilis. This B. subtilis-fermentation process of RYP increased the ratio of the active open-hydroxyl acid form and the prodrug lactone form of lovastatin, which is a potent cholesterol synthesis inhibitor. 3(2H)-benzofuranone was newly produced in the fermented red yeast rice product (FRYP) as analyzed by GC-MS. FRYP increased the free radical scavenging activity compared with RYP. FRYP blocked xanthine oxidase (XO)-induced oxidative cytotoxicity and inhibited the H O -induced intracellular ROS in cells. This is the first study to illustrate that B. subtilis-fermented FRYP is useful for facilitating the alteration in the physico-chemical property of lovastatin and enhancing antioxidant activity, which may have greater pharmacological activity.
[Mh] Termos MeSH primário: Bacillus subtilis
Produtos Biológicos
Suplementos Nutricionais
Lovastatina/química
[Mh] Termos MeSH secundário: Antioxidantes
Bacillus subtilis/metabolismo
Produtos Biológicos/metabolismo
Fermentação
Peróxido de Hidrogênio
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Biological Products); 0 (red yeast rice); 9LHU78OQFD (Lovastatin); BBX060AN9V (Hydrogen Peroxide)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170816
[Lr] Data última revisão:
170816
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170512
[St] Status:MEDLINE


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[PMID]:28353656
[Au] Autor:Yu Y; Lyu S; Chen D; Lin Y; Chen J; Chen G; Ye N
[Ad] Endereço:College of Horticulture, Key Laboratory of Tea Science, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China. 1130311016@fafu.edu.cn.
[Ti] Título:Volatiles Emitted at Different Flowering Stages of Jasminum sambac and Expression of Genes Related to α-Farnesene Biosynthesis.
[So] Source:Molecules;22(4), 2017 Mar 29.
[Is] ISSN:1420-3049
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Fresh jasmine flowers have been used to make jasmine teas in China, but there has been no complete information about volatile organic compound emissions in relation to flower developmental stages and no science-based knowledge about which floral stage should be used for the infusion. This study monitored volatile organic compounds emitted from living flowers of (L.) Ait. 'Bifoliatum' at five developmental stages and also from excised flowers. Among the compounds identified, α-farnesene, linalool, and benzyl acetate were most abundant. Since α-farnesene is synthesized through the Mevalonate pathway, four genes encoding 3-hydroxy-3-methylglutaryl coenzyme A synthase, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), farnesyl pyrophosphate synthase, and terpene synthase were isolated. Their expression patterns in living flowers at the five stages and in excised flowers coincided with the emission patterns of α-farnesene. Application of lovastatin, a HMGR inhibitor, significantly reduced the expression of the genes and greatly decreased the emission of α-farnesene. The sweet scent was diminished from lovastatin-treated flowers as well. These results indicate that α-farnesene is an important compound emitted from jasmine flowers, and its emission patterns suggest that flowers at the opening stage or flower buds 8 h after excision should be used for the infusion of tea leaves.
[Mh] Termos MeSH primário: Flores/crescimento & desenvolvimento
Jasminum/química
Proteínas de Plantas/metabolismo
Sesquiterpenos/metabolismo
Compostos Orgânicos Voláteis/análise
[Mh] Termos MeSH secundário: Flores/química
Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos
Regulação da Expressão Gênica de Plantas/efeitos dos fármacos
Jasminum/enzimologia
Lovastatina/farmacologia
Redes e Vias Metabólicas/efeitos dos fármacos
Óleos Vegetais/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Plant Oils); 0 (Plant Proteins); 0 (Sesquiterpenes); 0 (Volatile Organic Compounds); 502-61-4 (alpha-farnesene); 9LHU78OQFD (Lovastatin)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170518
[Lr] Data última revisão:
170518
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170330
[St] Status:MEDLINE


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[PMID]:28274099
[Au] Autor:Yao Q; Ma L; Liu L; Ikeda H; Fushinobu S; Li S; Xu LH
[Ad] Endereço:Ocean College, Zhejiang University, Dinghai, Zhoushan, Zhejiang 316021, P.R. China.
[Ti] Título:Hydroxylation of Compactin (ML-236B) by CYP105D7 (SAV_7469) from .
[So] Source:J Microbiol Biotechnol;27(5):956-964, 2017 May 28.
[Is] ISSN:1738-8872
[Cp] País de publicação:Korea (South)
[La] Idioma:eng
[Ab] Resumo:Compactin and pravastatin are competitive cholesterol biosynthesis inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase and belong to the statin drugs; however, the latter shows superior pharmacokinetic characteristics. Previously, we reported that the bacterial P450, CYP105D7, from can catalyze the hydroxylation of 1-deoxypentalenic acid, diclofenac, and naringenin. Here, we demonstrate that CYP105D7 could also catalyze compactin hydroxylation in vitro. In the presence of both bacterial and cyanobacterial redox partner systems with an NADPH regeneration system, the reaction produced two hydroxylated products, including pravastatin (hydroxylated at the C6 position). The steady-state kinetic parameters were measured using the redox partners of putidaredoxin and its reductase. The and values for compactin were 39.1 ± 8.8 µM and 1.12 ± 0.09 min , respectively. The / value for compactin (0.029 min ·µM ) was lower than that for diclofenac (0.114 min-1·µM ). Spectroscopic analysis showed that CYP105D7 binds to compactin with a value of 17.5 ± 3.6 µM. Molecular docking analysis was performed to build a possible binding model of compactin. Comparisons of different substrates with CYP105D7 were conclusively illustrated for the first time.
[Mh] Termos MeSH primário: Sistema Enzimático do Citocromo P-450/metabolismo
Lovastatina/análogos & derivados
Streptomyces/metabolismo
[Mh] Termos MeSH secundário: Biotecnologia/métodos
Domínio Catalítico
Sistema Enzimático do Citocromo P-450/química
Ferredoxinas/metabolismo
Hidroxilação
Cinética
Lovastatina/metabolismo
Simulação de Acoplamento Molecular
Oxirredução
Pravastatina/química
Pravastatina/metabolismo
Espectrofotometria Ultravioleta
Streptomyces/enzimologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ferredoxins); 1UQM1K0W9X (mevastatin); 57087-75-9 (putidaredoxin); 9035-51-2 (Cytochrome P-450 Enzyme System); 9LHU78OQFD (Lovastatin); KXO2KT9N0G (Pravastatin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170310
[St] Status:MEDLINE
[do] DOI:10.4014/jmb.1610.10079


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[PMID]:28212283
[Au] Autor:Chin KY; Abdul-Majeed S; Mohamed N; Ima-Nirwana S
[Ad] Endereço:Department of Pharmacology, Universiti Kebangsaan Malaysia Medical Centre, Cheras 56000, Malaysia. chinkokyong@ppukm.ukm.edu.my.
[Ti] Título:The Effects of Tocotrienol and Lovastatin Co-Supplementation on Bone Dynamic Histomorphometry and Bone Morphogenetic Protein-2 Expression in Rats with Estrogen Deficiency.
[So] Source:Nutrients;9(2), 2017 Feb 15.
[Is] ISSN:2072-6643
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Both tocotrienol and statins are suppressors of the mevalonate pathway. Supplementation of tocotrienol among statin users could potentially protect them against osteoporosis. This study aimed to compare the effects of tocotrienol and lovastatin co-supplementation with individual treatments on bone dynamic histomorphometric indices and bone morphogenetic protein-2 (BMP-2) gene expression in ovariectomized rats. Forty-eight female Sprague-Dawley rats were randomized equally into six groups. The baseline was sacrificed upon receipt. All other groups were ovariectomized, except for the sham group. The ovariectomized groups were administered orally daily with (1) lovastatin 11 mg/kg/day alone; (2) tocotrienol derived from annatto bean (annatto tocotrienol) 60 mg/kg/day alone; (3) lovastatin 11 mg/kg/day, and annatto tocotrienol 60 mg/kg/day. The sham and ovariectomized control groups were treated with equal volume of vehicle. After eight weeks of treatment, the rats were sacrificed. Their bones were harvested for bone dynamic histomorphometry and BMP-2 gene expression. Rats supplemented with annatto tocotrienol and lovastatin concurrently demonstrated significantly lower single-labeled surface, but increased double-labeled surface, mineralizing surface, mineral apposition rate and bone formation rate compared to individual treatments ( < 0.05). There was a parallel increase in BMP-2 gene expression in the rats receiving combined treatment ( < 0.05). The combination of annatto tocotrienol and lovastatin exerted either additively or synergistically on selected bone parameters. In conclusion, tocotrienol can augment the bone formation and mineralization in rats receiving low-dose statins. Supplementation of tocotrienol in statin users can potentially protect them from osteoporosis.
[Mh] Termos MeSH primário: Proteína Morfogenética Óssea 2/metabolismo
Osso e Ossos/efeitos dos fármacos
Suplementos Nutricionais
Estrogênios/deficiência
Lovastatina/administração & dosagem
Tocotrienóis/administração & dosagem
[Mh] Termos MeSH secundário: Animais
Bixaceae/química
Osso e Ossos/metabolismo
Carotenoides/química
Feminino
Ovariectomia
Extratos Vegetais/química
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bmp2 protein, rat); 0 (Bone Morphogenetic Protein 2); 0 (Estrogens); 0 (Plant Extracts); 0 (Tocotrienols); 36-88-4 (Carotenoids); 6PQP1V1B6O (annatto); 9LHU78OQFD (Lovastatin)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170619
[Lr] Data última revisão:
170619
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170218
[St] Status:MEDLINE



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